This project explores the nature of antibody responses to CD4 and the possible application of such antibodies as an idiotypic vaccine for AIDS. Anti-idiotypic antibodies have been shown to induce protective immunity to a variety of diseases in animals, and so this approach should be explored for AIDS. Such a vaccine would have the advantage that immunity induced would cross-react with all HIV variants, and the vaccine would be safe and easy to prepare. In order to derive appropriate anti-CD4 antibodies, responses to CD4 must be better understood. Specific projects include: 1) We have continued studies of anti-Leu3a as a potential idiotypic vaccine for AIDS. Contrary to reports in the literature, our results indicate that anti-Leu3a is a not candidate for an idiotypic vaccine for AIDS, even when conjugated to carrier by the same methods reported. 2) We have developed two site-specific assays for the gpl2O binding site on CD4. In one, antibodies are tested for ability to inhibit the binding of recombinant gpl2O (rgpl2O) to MOLT-4 cells, with detection by rabbit anti-- gpl2O serum and FITC-goat anti-rabbit IgG. The second assay measures inhibition of binding of CD4-IgG to solid phase rgpl2O, with detection by biotinylated goat anti-human IgG and avidin-peroxidase. 3) Using these new assays, we can evaluate immune responses to a particular determinant on CD4, namely the gpl2O binding site. Comparative studies are in progress addressing the immunogenicity of this site in the following situations: a. Immunization with rCD4; b. Immunization with human T cells such as MOLT-4; c. Immunization using different responding strains of mice to examine genetic control of responsiveness;